In newborn hamsters, rats and cats, corticospinal axons grow around a lesion of their pathway, but brainstem-spinal axons do not. In the North American opossum, however, axons from the red nucleus of the brainstem are able to circumvent a lesion of their pathway if it is inflicted early enough in development. It is our hypothesis that all brainstem-spinal axons can grow around a lesion of their pathway at some stage of development and that the axons which lose that ability first are the ones which grow into the spinal cord the earliest. In our first specific aim we propose to establish whether axons from specific reticular and vestibular nuclei grow around a lesion of their pathway in the opossum and, if so, to determine if they lose that ability before rubrospinal axons. The above axons were chosen for study because they grow into the spinal cord earlier than axons from the red nucleus and their known laterality makes it possible to interpret the results of experimental manipulation. If growth around a lesion can be documented, we will determine whether it results from regeneration of cut axons, the addition of new axons, or both. Ascending spinal axons also fail to grow around a lesion of their pathway in newborn rats. We hypothesize, however, that they are capable of doing so during earlier stages of development and that some lose that ability before others. In our second specific aim we propose to establish whether dorsal root axons of the fasciculus gracilis and axons of Clarke's nucleus grow around a lesion of their pathway in developing opossums and, if so, to determine whether the critical periods for their plasticity are different. If plasticity can be documented, we will determine whether it results from regeneration of cut axons, new growth, or both. The above axons were chosen for study because of their different timetables for development. Since it is possible that the ability of axons to grow around a lesion depends upon synthesis and transport of growth associated proteins, we propose to study the developmental expression of one such protein, GAP-43, and its corresponding mRNA in rubrospinal neurons to determine if they decrease or cease to be expressed at the end of the critical period for plasticity. Our project addresses some of the same issues as Projects 3 and 5.